Methods for the diagnosis and ablation treatment of ventricular tachycardia

ABSTRACT

A closed-heart method for treating ventricular tachycardia in a myocardial infarct patient afflicted with ventricular tachycardia is disclosed. The method comprises, first, defining a thin layer of spared myocardial tissue positioned between the myocardial infarct scar tissue and the inner surface of the myocardium (the endocardium) of the patient, and then ablating the thin layer of spared myocardial tissue by a closed-heart procedure with an ablation catheter. Apparatus for carrying out the method is also disclosed, 
     Also disclosed is a method for prognosing the likelihood of ventricular tachycardia occuring in a myocardial infarct patient not previously diagnosed as afflicted with ventricular tachycardia. The method comprises detecting a thin layer of spared myocardial tissue positioned between the myocardial infarct scar tissue and the inner surface of the myocardium (the endocardium) in the patient.

This invention was made with Government support under grant numbersHL-28429, HL-17670, and HL-33637 from the National Institutes of Healthand grant number CDR-8622201 from the National Science Foundation. TheGovernment has certain rights to this invention.

This application is a continuation of copending application Ser. No.07/829,457, filed 31 Jan. 1992, now U.S. Pat. No. 5,222,501, thedisclosure of which is incorporated by reference herein in its entirety.

FIELD OF THE INVENTION

This invention relates to methods for the ablation of cardiac tissue forthe treatment of ventricular tachycardia and to diagnostic methods fordetecting conditions which indicate a high risk of ventriculartachycardia.

BACKGROUND OF THE INVENTION

Ventricular tachycardia is a disease of the heart in which the heart'snormal rhythmic contraction is altered, thus affecting heart function.The condition is often described as a heart beat which is too fast,although the disease is far more complex. Ventricular tachycardia occursmost often in patients following a myocardial infarction. A myocardialinfarction, commonly referred to as a heart attack, is a loss of bloodflow to a region of the heart causing the myocardial (muscle) tissue inthat region to die and be replaced by an area of scar tissue known as amyocardial infarct. In most cases, this occurs in the left ventricle.

Ventricular tachycardia ("VT") may be initiated and sustained by are-entrant mechanism, termed a "circus" movement. The mechanism ofre-entry, as it is currently understood, is discussed in M. Josephsonand H. Wellens, Tachycardias: Mechanisms, Diagnosis, Treatment, Chap. 14(1984) (Lea & Febiger). Most cases of sudden cardiac death that haveoccurred during cardiac monitoring have begun as VT that degeneratedinto ventricular fibrillation.

While VT can be halted after it begins by pacing or cardioversion, it ispreferable to prevent the arrhythmia from arising. Drug therapy has beenused, but is successful in only 30 to 50 percent of patients and hasundesirable side effects. Endocardial resection, a surgical procedureinvolving removing the tissue in the ventricle thought to be the sourceof the VT, has been reported to eradicate VT in up to 90 percent ofpatients, but it suffers from a 5 to 10 percent incidence ofperioperative mortality. For a discussion of surgical procedures, see T.Ferguson and J. Cox, Surgical Therapy for Cardiac Arrhythmias, inNonpharmacological Therapy of Tachyarrhythmias (G. Breithardt et al.eds. 1987).

As an alternative to surgery, the technique most often attempted isablation. Typically, programmed premature pacing is performed from acatheter electrode in the right or left ventricular cavity. Duringprogrammed premature pacing, a stimulus, usually of twice diastolicthreshold, is repeatedly given prematurely until either VT is induced orthe tissue is too refractory to be excited. The ECG is examined duringinduced VT and compared to the ECG showing spontaneous bouts of VT. Ifthe ECG is similar, it is assumed that the patient's clinical VT isbeing induced. A mapping catheter in the left ventricular cavity is usedto record from numerous sites sequentially to determine the activationsequence along the left ventricular endocardium during the induced VT.The site from which activation appears to originate during the inducedVT is identified and assumed to be a portion of the reentrant pathway.The techniques of pace mapping and entrainment may then be used in anattempt to confirm or refine the localization of the region rising toVT. The region is then ablated. Unfortunately, this technique is usuallyunsuccessful unless repeated many times. For example, it has beenreported by Downar et al. that for a similar technique (the electrodeswere located on an endocardial balloon instead of a catheter), anywherefrom 10 to 42 shocks through different electrodes were required toprevent the reinduction of VT. It is assumed that failures occur becauseablation is not performed at the correct site or does not create alesion deep enough within the ventricular wall to reach the reentrantpathway.

It is extremely desireable to prognose the likelihood of a myocardialinfarct patient being susceptible to ventricular tachycardia. U.S. Pat.No. 4,680,708 to M. Cain and B. Sobel suggests a method and apparatusfor analyzing electrocardiogram signals to prognose ventriculartachycardia, but the early detection of myocardial infarct patientssusceptible to ventricular tachycardia remains a problem.

In view of the foregoing, an object of the present invention is toprovide a technique which is effective in combatting VT, does notrequire the administration of drugs, and does not require open-heartsurgery.

A further object of the present invention is to provide a means forprognosing the likelihood of ventricular tachycardia occuring in amyocardial infarct patient not previously diagnosed as havingventricular tachycardia.

SUMMARY OF THE INVENTION

The present invention is based on the concept that a thin layer ofviable myocardial tissue adjacent to the endocardium in a myocardialinfarct patient is capable of supporting multiple re-entrant pathways,any one of which can give rise to ventricular tachycardia.

In view of the foregoing finding, a first aspect of the presentinvention is a closed-heart method for treating ventricular tachycardiain a myocardial infarct patient afflicted with ventricular tachycardia.The method comprises, first, defining a thin layer of spared myocardialtissue positioned between the myocardial infarct scar tissue and theinner surface of the myocardium (the endocardium) of the patient, andthen ablating the thin layer of spared myocardial tissue by aclosed-heart procedure with an ablation catheter.

In a particular embodiment of the foregoing, the ablating step iscarried out by creating at least one elongate lesion in said thin layerextending from the endocardium to the myocardial infarct scar tissue ina closed-heart procedure with an ablation catheter. The at least oneelongate lesion is configured to reduce the size, in surface area, ofany portion of the thin layer in electrical contact with the remainderof the endocardium sufficient to combat ventricular tachycardia in saidpatient. This may be carried out by electrically separating from theremainder of the endocardium a portion of the thin layer which has asize, in surface area, sufficient to combat ventricular tachycardia(e.g., by creating a continuous elongate lesion around the thin layer ofspared myocardial tissue, the continuous lesion encircling the thinlayer to electrically separate the thin layer from adjacent myocardialtissue), or by creating at least one (or a plurality) of elongatelesions in the thin layer, wherein the at least one elongate lesiondivides the layer into a plurality of electrically separated portions,with the capability of each portion for originating ventriculartachycardia being reduced sufficiently to combat ventricular tachycardiain the patient.

Another aspect of the present invention is an apparatus for the ablationtreatment of ventricular tachycardia. The apparatus comprises anintraventricular catheter, a detecting means for detecting a thin layerof spared endocardial tissue connected to the intraventricular catheter,an ablation means for ablating the thin layer of spared endocardialtissue connected to the intraventricular catheter; and an analyzingmeans operatively associated with the detecting means for prognosing thelikelihood of ventricular tachycardia arising from the thin layer.

Another aspect of the present invention is a method for prognosing thelikelihood of ventricular tachycardia occuring in a myocardial infarctpatient not previously diagnosed as afflicted with ventriculartachycardia. The method comprises detecting a thin layer of sparedmyocardial tissue positioned between the myocardial infarct scar tissueand the inner surface of the myocardium (the endocardium) in thepatient.

Previous work in the diagnosis and treatment of ventricular tachycardiahas always looked for functional or electrical characteristics of tissuerather than a specific anatomic structure. The present invention, incontrast, is based on the finding that a specific macroscopic anatomicalstructure gives rise to ventricular tachycardia.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a side view of a human heart, with portions cut away to revealthe internal chambers and myocardial walls.

FIG. 2 illustrates typical cross-sectional slices from control (FIG.2A), subacute ventricular tachycardia (FIG. 2B), and chronic ventriculartachycardia (FIG. 2C) groups.

FIG. 3 schematically illustrates various ablation patterns on theinternal surface of the heart which may be employed in carrying out thepresent invention.

FIG. 4 schematically illustrates an apparatus useful for carrying outthe ablation method of the present invention.

FIGS. 5-6 illustrate the use of an apparatus as given in FIG. 4.

FIG. 7 shows the initiation of sustained ventricular tachycardiasettling into a monomorphic figure of 8 reentry pattern. The activationtimes and isochronal maps of the last beat of the S1 train (Panel A) areshown as well as the first 5 beats of VT (Panels B-F) induced after a 20mA S2 stimulus at an S1S2 interval of 210 ms as recorded by a plague of121 bipolar electrodes over the infarct in the left ventricle. The S1S1interval of the pacing train is 300 ms. The long axis of the sparedmyocardial fibers is represented by the double headed arrow at the topof the figure. Each number gives the activation time in ms at anelectrode site. The isochronal interval is 20 ms. In panel A time zerois the beginning of the S1 stimulus. In Panels B-F time zero is thebeginning of the S2 stimulus. In panel B, the first beat after S2stimulation, arrows indicate that the activation fronts conduct aroundboth sides of a line of block (represented by the heavy black bar inthis and subsequent figures). The hatched line (in this and subsequentfigures) represents a frame line between panels in which reentry isbelieved to occur. In panel C, the adjoining solid and hatched linesindicate block between beats one and two and reentry between beats twoand three respectively. Panel 2 shows the monomorphic ventriculartachycardia as recorded by the surface leads I, II and III. Closed arrowindicates S2.

FIG. 8 shows the initiation of sustained monomorphic ventriculartachycardia with a figure of 8 reentry pattern in a second animal inwhich the S1 was delivered from the right ventricular free wall. Theactivation times and isochronal maps of the last beat of the 300 ms S1train (Panel A) as well as those of the first 3 beats of ventriculartachycardia (Panels B-D) induced by a 30 mA S2 stimulus at an S1S2interval of 230 ms are shown. In panel B, the activation pattern of thefirst beat post S2 stimulation is compatible with figure of 8 reentry.The initial activation sequence is directed back toward the S1stimulation site in the direction opposite the S1 activation sequence.Figure of 8 reentry is also seen in the subsequent beats of ventriculartachycardia (Panels C and D). Panel E shows the lead II rhythm strip ofventricular tachycardia induced. Open arrow indicates the first S1 andclosed arrow indicates S2. The long axis of the spared myocardial fibersis represented by the double headed arrow at the top of the figure.

FIG. 9 shows the initiation of sustained monomorphic ventriculartachycardia with a figure of 8 reentry pattern in which the S1 wasdelivered from the left ventricular free wall in the same animal as forFIG. 8. The activation times and isochronal maps, of the last beat ofthe 300 ms S1 train (Panel A) as well as those of the first 3 beats ofventricular tachycardia (Panels B-D) induced by a 30 mA S2 stimulus atan S1S2 interval of 230 ms, are shown. In panel B, the activationpattern of the first beat post S2 stimulation is compatible with figureof 8 reentry and once again the initial activation is generally backtoward the S1 stimulation site in the direction opposite the S1activation sequence. Figure of 8 reentry is also seen in subsequentbeats (Panels C and D). Panel E shows the lead II rhythm strip ofventricular tachycardia induced. Open arrow indicates the first S1 andclosed arrow indicates S2.

DETAILED DESCRIPTION OF THE INVENTION

The basic anatomy of the human heart 10 is illustrated in FIG. 1. Itswalls are composed primarily of myocardial (muscle) tissue. The muscletissue walls of the heart are referred to as the myocardium 11. Theinner surface of the myocardium, which is in contact with the blood inthe heart chambers, is the endocardium 12,12'. The heart islongitudinally divided into left and right halves. Each half has anupper chamber called an atrium 13,14 and a lower chamber called aventricle 15,16. Between the atrium and the ventricle of each half is anatrioventricular (AV) valve 17 which is a one way valve allowing bloodflow only from the atrium into the ventricle. The right and leftventricles are separated by the interventricular septum 18.

The circulatory system is comprised of two separate systems, pulmonaryand systematic circulation. In the pulmonary circuit blood is pumped bythe right ventricle 15 into the pulmonary artery which then splits intoa right pulmonary artery 20 and a left pulmonary artery 21 allowing toflow through the lungs and then into the pulmonary veins 22,23,24,25which flow into the left atrium 14. The oxygen rich blood from thepulmonary circuit is pumped by the left ventricle into the systemiccircuit via the aorta. After passing throughout the body, the bloodreturns to the right atrium via the inferior vena cava and the superiorvena cava.

The thickness of the walls of the chambers of the hearts vary inrelation to the amount of pumping work they perform. The atria 13, 14are of little importance in pumping the blood except under high demandconditions, such as exercise, and are thin walled (2-3 millimeters). Theright ventricle 15 only pumps blood through the relatively shortpulmonary circuit and is significantly more thin walled than the leftventricle 16 which must maintain the pressure within the systemiccircuit (8-12 millimeters).

FIG. 2 illustrates typical cross-sectional slices of ventricles frompatients with myocardial infarction but no ventricular tachycardia(control) (FIG. 2A), patients with subacute myocardial infarction withventricular tachycardia (FIG. 2B), and patients with chronic myocardialinfarction with ventricular tachycardia (FIG. 2C) groups. The subacutegroup had predominantly large solid myocardial infarcts 30 with ribbonspared subendocardium 31. The chronic ventricular tachycardia group haspredominantly large patchy myocardial infarcts 32 with irregular sparedsubendocardium. The control group had smaller hearts and smaller morerandomly distributed patchy myocardial infarcts 34 with little ribbonspared subendocardium 35. Black represents solid myocardial infarct, andstippling represents patchy myocardial infarct. Slices are seen from thebasal aspect. These data are known. See D. Bolick et al., Circulation74, 1266, 1273 (1986).

The thin layer referred to herein is a layer of surviving myocardialtissue located between the surface of the endocardium 12,12' and themyocardial infarct scar tissue. The thin layer may be in the right orleft ventricle, but more typically the left ventricle. A layer offibrosis may be positioned beneath the thin layer, as explained below.While the precise dimensions of the thin layer will vary from patient topatient, with some variability due to the variability of the infarct inthe epicardial to endocardial dimension, the thin layer will generallyhave a thickness of up to about 5 millimeters, and will generally havean endocardial surface area of at least 15 square centimeters.Typically, the thin layer will have a thickness of from about 0.25 to 2millimeters, and will have an endocardial surface area of from about 20to 40 square centimeters.

The present invention is directed to both diagnostic and treatmentmethods for ventricular tachycardia in a patient afflicted with amyocardial infarct. The treatment method of the present inventioninvolves first, defining a thin layer of spared myocardial tissuepositioned between the myocardial infarct scar tissue and the innersurface of the myocardium (the endocardium) of the patient, and thenablating the thin layer of spared myocardial tissue. The diagnosticmethod provides a means for examining myocardial infarct patients todetermine their risk of developing ventricular tachycardia by detectingthe presence of a thin layer of spared myocardial tissue positionedbetween the myocardial infarct scar tissue and the inner surface of themyocardium (the endocardium).

Reentrant pathways causing VT may arise from numerous sites within thethin layer of spared tissue between the infarct and the endocardium, thefirst or defining step involves identifying the presence and location ofthis thin layer instead of inducing and mapping the activation sequenceduring a particular incidence of induced VT as was done previously.Thus, the subject on which the defining step is performed need not haveVT induced prior to the procedure, and need not be in VT during thedefining step.

The thin layer can be defined by any one or a combination of severaltechniques, including (1) analyzing recordings during regular rhythmfrom electrodes on a catheter; (2) pacing from an electrode on thecatheter and analyzing the pacing threshold as well as recordings of thepacing stimulus and the ensuing activation sequence from otherelectrodes on the same catheter; (3) direct visualization of the thinlayer of spared myocardial tissue by an imaging technique such asechocardiography/ultrasound which can differentiate healthy myocardialtissue from infarcted tissue; (4) detecting by echocardiography theinfarct itself overlying the thin layer of spared myocardial tissue(e.g., by detecting altered heart wall motion overlying the infarct orby detecting altered backscatter from the infarct); (5) visualization ofendocardial fibrosis beneath the thin layer of spared myocardial tissue(i.e., between the thin layer of spared myocardial tissue and theventricular cavity); and (6) electrically stimulating the endocardium todetect an increased pacing threshold (due to the presence of endocardialfibrosis overlying the thin layer of spared myocardial tissue).

Any suitable apparatus may be employed to carry out the defining step,such as a catheter mounted echocardiographic ultrasound crystal sensorinserted into the interior of the heart of said patient, anechocardiographic ultrasound crystal sensor positioned in the esophagusof the patient, or echocardiographyic ultrasound crystal sensor appliedto the chest wall by contact to the skin. The imaging device need not beon a catheter (is in the case of an esophageal echocardiograph), thoughpreferably the mapping is performed with a catheter mounted sensingdevice. Particularly suitable is an echocardiagraphic/ultrasound crystalsensor mounted on a catheter which is inserted into the interior of theheart of the patient. This same catheter can also carry the ablationdevice as discussed below. Suitable detection devices are known,examples of which are disclosed in U.S. Pat. No. 5,000,185 and in PCTApplication Number WO 91/02488. (Applicants intend that all U.S. Patentreferences cited herein be incorporated herein by reference). Anultrasonic technique for mapping myocardial tissue with an externalsensor is discussed in B. Barzilai et al., J. Am. Soc. Echo. 1, 179-186(1988)(showing altered backscatter from myocardial infarct).

Once the thin layer of spared myocardium is identified, it can beablated by a variety of methods. Three such methods of the presentinvention, along with prior art methods, are schematically illustratedin FIG. 3. The endocardial surface is schematically illustrated in FIG.3A, the prior art surgical resection technique is illustrated in FIG.3B, and prior art catheter ablation techniques are schematicallyillustrated in FIG. 3C. In the embodiment of the invention illustratedin FIG. 3D, ablation is accomplished by creating a continuous lesion 41extending from the endocardium to the myocardial infarct scar tissuearound the thin layer of spared myocardial tissue. This continuouslesion encircling the thin layer electrically isolates the thin layerfrom adjacent myocardial tissue so that any arrhythmias arising in thethin layer are not able to propagate into the rest of the heart. In theembodiment of the invention illustrated in FIG. 3E, ablation isaccomplished by creating at least one, or as illustrated a plurality of,elongate lesions 42 in the thin layer, with each lesion extending fromthe endocardium to the myocardial infarct scar tissue. The elongatelesion(s) are patterned to divide the thin layer into a plurality ofelectrically separated portions each, of which is substantiallyincapable of originating ventricular tachycardia. In the embodiment ofthe invention illustrated in FIG. 3F, ablation is accomplished bydestroying all of the thin layer of spared myocardial tissue with alarge lesion 43.

A variety of devices are known and available for performing the ablationstep. A direct current ablation electrode such as that disclosed in U.S.Pat. No. 4,896,671 or a laser ablation catheter such as that disclosedin U.S. Pat. No. 4,985,028 may be used. More preferably, a radiofrequency (RF) ablation catheter as disclosed in U.S. Pat. No. 4,945,912or a microwave ablation catheter such as that discussed in J. Langberget al., Pace 14, 2105 (December, 1991) is used. Another approach is toablate the thin layer with ultrasound at high energy, as discussed ingreater detail below.

As noted above, both the detecting means such as anechocardiagraphic/ultrasound crystal sensor and an ablation means suchas a laser unit may advantageously be located on the same catheter.Examples of such catheter devices are disclosed in U.S. Pat. No.5,000,185, U.S. Pat. No. 4,936,281 and in PCT Application Number WO91/02488. A schematic diagram of such a catheter device using andultrasound sensing means and a laser ablation means is shown in FIG. 4.The system 50 includes a catheter probe assembly 51 including a distalsubassembly 52 inserted within a guide catheter 53. The proximal end ofthe guide catheter 53 is coupled to a conventional side arm connector54. The distal subassembly 52 is coupled to a suitable motor means 55which provides the drive to maneuver the distal subassembly 52. Theultrasonic imaging components within the distal subassembly 52 areelectrically connected with an electroacoustic transducer and anultrasound transceiver 56 via suitable electrical contact brushes 57. Toperform detection the ultrasonic imaging components within the distalsubassembly are activated and the received signals are processed by theultrasound transceiver 56. The signals are further processed byalgorithms performed by the computer 58 to generate an image of thetissue structures reflecting the ultrasonic energy toward the distalsubassembly 52. The ablating is performed by a laser means. A laserdriver 60 provides a source of laser radiation which passes via thecontact brushes 57 to a dual function electrical/optical connector 61which couples the ultrasonic imaging components and laser opticalcomponents within the distal subassembly 52 to the ultrasoundtransceiver 56 and the laser driver 60. The computer 58 also functionsto allow the operator to control the laser driver to perform ablation oftissue where desired.

A software program running in the computer 58, which computer isoperatively associated with the detecting means, provides a means forprognosing the likelihood of ventricular tachycardia arising from saidthin layer. In a typical embodiment of this method, the detecting stepincludes determining if a thin layer of spared tissue exists between theinfarct scar tissue and the endocardium, then creating an anatomical mapof the locations of the thin layer identified to define the thin layerareas, and then evaluating the dimensions of the thin layer areas todetermine if the contiguous portions of these areas are of sufficientsize to support reentrant pathways.

Another option in an apparatus of the present invention is, as notedabove, to use ultrasound energy at higher power levels to ablate thethin layer of tissue. An intraventricular catheter for accomplishingthis method would have two sets of ultrasound crystal connected thereto:one set configured for detecting the thin layer, and another setconfigured for ablation of the thin layer.

FIGS. 5-6 illustrate the use of a catheter of FIG. 4 in a method of thepresent invention. The catheter 51 is first introduced into thecirculatory system, preferably through a vessel in the leg, and advancedinto the heart 10. In the typical case of a patient suffering from VTfollowing a myocardial infarction, the infarct scar tissue is located inthe left ventricle 16, either within the outer walls of the ventricle orwithin the interventricular septum 18. In such a patient, the catheteris advanced into the left ventricle 16, for example by advancing thecatheter into the femoral artery and then through the aorta 26 into theleft ventricle 16. The detecting means is then activated and thecatheter is manipulated substantially throughout the left ventricle 16to locate any areas of thin layers of surviving tissue between theendocardium 12 and the infarct scar tissue. Preferably, this informationis generated for substantially the entire area affected and then thecatheter is withdrawn.

In the treatment of the present invention, each thin layer area locatedis rendered substantially incapable of supporting VT by the ablatingstep. The ablating step may be performed for all the thin layer areasfound after the mapping is completed or, more preferably, is performedon each contiguous thin layer area once the area is defined. Theportions of tissue to be ablated depends upon the embodiment of thepresent invention utilized as was discussed previously.

The ablating step is optionally followed by the step of verifying thatthe thin layer of spared myocardial tissue is no longer capable oforiginating a ventricular tachycardia. This verifying step can beaccomplished using a programmed pacing technique to induce ventriculartachycardia. Such techniques are discussed in M. Josephson and H.Wellens, Tachycardias: Mechanisms, Diagnosis, Treatment, Chap. 14,(1984).

As noted above, the present invention further provides a method forprognosing the likelihood of ventricular tachycardia occuring in amyocardial infarct patient not previously diagnosed as afflicted withventricular tachycardia. The method comprises detecting a thin layer ofspared myocardial tissue positioned between the myocardial infarct scartissue and the inner surface of the myocardium (the endocardium) in thepatient. The thin layer to be detected is described in detail above. Theprocedure is advantageously carried out by closed-heart procedures, asdiscussed in detail above. In a typical embodiment of this method, thedetecting step includes determining if a thin layer of spared tissueexists between the infarct scar tissue and the endocardium, thencreating an anatomical map of the locations of the thin layer identifiedto define the thin layer areas, and then evaluating the dimensions ofthe thin layer areas to determine if the contiguous portions of theseareas are of sufficient size to support reentrant pathways.

The present invention is explained further in the following Example.This Example is illustrative of the present invention, and is not to beconstrued as limiting thereof.

EXAMPLE 1 High Current Stimuli to the Spared Epicardium of a LargeInfarct Induce Ventricular Tachycardia

This study was carried out to test the hypothesis that a high currentpremature stimulus during the vulnerable period over the survivingepicardium of a four day old infarct in a canine model will inducesustained VT rather than ventricular fibrillation. As explained indetail below, it was found that a large S2 over a nontransmural infarctinduced VT if the spared myocardium was thin.

Materials and Methods Surgical Preparation

In twelve mongrel dogs, anesthesia was induced using intravenousthiopental sodium, 20 mg/kg, and maintained using a continuous infusionof thiopental sodium at a maintenance rate of approximately 0.8mg/kg/min. Succinylcholine, 1 mg/kg, was also given at the time ofanesthesia induction. The animals were intubated with a cuffedendotracheal tube and ventilated with room air and oxygen through aHarvard respirator (Harvard Apparatus Co. South Natick, Mass.). Afemoral arterial line and two intravenous lines were inserted usingsterile techniques. Systemic arterial pressure was continuouslydisplayed. Arterial blood samples were drawn every 30-60 min fordetermination of pH, PO2, PCO2, base excess, bicarbonate, Na⁺, K⁺, andCa⁺⁺ content. Ringer's lactate was continuously infused via a peripheralintravenous line. This was supplemented with sodium bicarbonate,potassium chloride, and calcium chloride as indicated to maintain pH andelectrolytes within normal values. Electrocardiographic leads wereapplied for continuous ECG monitoring. Body temperature was maintainedwith a thermal mattress. With sterile surgical techniques the heart wasexposed through a left thoracotomy at the fourth intercostal space; thepericardium was opened, and the left anterior descending coronary (LAD)artery was dissected free at the tip of the left atrial appendage. Anoose occluder was placed around the left anterior descending artery andit was occluded by the Harris two state procedure (A. Harris and A.Rojas, Exp. Med. Surg. 1, 105 (1943)). In order to ensure sparing of theepicardium in the entire infarct zone, partial occlusion was maintainedfor 30 min, followed by complete occlusion for 90 min prior toreperfusion. Five minutes before initiation of partial occlusion andagain before the termination of complete occlusion the animals werepre-treated with bolus injections of intravenous lidocaine (2 mg/kg). Asecond bolus of lidocaine (1 mg/kg) was administered ten minutes later.The chest was closed in layers, evacuated under negative pressure andthe animal was allowed to recover.

Four days after LAD occlusion, anesthesia was induced with intravenouspentobarbital (30-35 mg/kg body weight) and maintained with a continuousinfusion of pentobarbital at a rate of approximately 0.05 mg/kg per min.Succinylcholine (1 mg/kg) was also given intravenously at the time ofanesthesia induction. Supplemental doses of 0.25 of 0.5 mg/kg ofsuccinylcholine were given hourly as needed to maintain musclerelaxation. The animals were ventilated, hemodynamically monitored andmaintained as described above. A median sternotomy was performed, andthe heart was suspended in a pericardial cradle. The recording apparatusconsisted of 121 bipolar Ag-AgCl epicardial electrodes (see F. Witkowskiand P. Penkoske, Am. J. Physiol. 254, H804 (1988)) arranged in 11columns and 11 rows mounted in a 4×4 cm plaque. Each epicardialelectrode was 1 mm in diameter. There was a 2 mm intra-electrodedistance between each member of the bipolar pair and an inter-electrodedistance of 4 mm. This plaque also contained a centrally locatedstimulating electrode. The plaque of epicardial recording electrodes wassutured over the infarcted anterior surface of the left ventricle. Foursolid stainless steel wires (American Wire Gauge #30, Cooner Wire Co.Chatsworth, Calif.) that were insulated except at the tip werepositioned for S1 pacing from the lateral right ventricle, the rightventricular outflow tract, the lateral left ventricle and the posteriorleft ventricle. Defibrillating patches were sutured over the rightatrium and upper portion of the lateral right ventricle and theposterior apical left ventricle to deliver cardioversion ordefibrillation shocks. Limb leads I, II and III were recorded with limblead II filtered from 50 Hz to 300 Hz so it recovered quickly afterlarge premature stimuli.

Data Acquisition

A computer assisted-mapping system capable of simultaneously recording128 channels was used to record the stimulus potentials in unipolar modewith the left leg as reference and the activation complexes in bipolarmode. See P. Wolf et al., A Method of Measuring Cardiac DefibrillationPotentials, Proc. ACEMB Baltimore, Md., 4 (1986)(The Alliance forEngineering in Medicine and Biology, Publishers). Signals were recordeddigitally at a rate of 1,000 samples per second with a low pass filterat 500 Hz and the high-pass filter at 5 Hz. See W. Smith et al.,Proceedings of Computers in Cardiology, 131 (1982)(IEEE ComputerSociety). Gain settings for each channel were individually adjusted foroptimum recording. The data were stored on videotape for off-lineanalysis. See P. Wolf et al., Proc. ACEMB Washington, D.C., 124 (1985).The recordings from each channel were subsequently displayed on a SUN3/60 work station to allow measurement of stimulus potentials anddetection of activation times.

Definitions

The ventricular refractory period for a particular strength S2 wasdefined as the largest S1-S2 interval that failed to evoke a ventricularresponse. In this study inducible sustained monomorphic ventriculartachycardia was defined as an ECG sequence of uniform ventriculardepolarizations at a cycle length of less than 400 ms, that lasted morethan 30 sec or produced hemodynamic compromise requiring immediatecardioversion.

Stimulation Protocol

Unipolar cathodal pacing at a pulse width of 5 ms was used to determinelate diastolic threshold at each of the five stimulation sites (tworight ventricular sites, two left ventricular sites and the center ofthe recording plaque). The propensity for sustained ventriculartachycardia was assessed by pacing at a cycle length of 300 ms for 10beats (S1) at twice diastolic threshold followed by an extra stimulus(S2) consisting of a 5 ms square wave which was given to scan diastoleat 5 ms intervals or less. The S1 train was delivered from one of thefour pacing sites outside of the plaque of recording electrodes, whileS2 was always delivered from the center of the plaque. Diastole wasscanned by decreasing the S1S2 coupling interval in steps of 5 ms. Theinitial strength of the S2 was 10 mA. If diastole was scanned withoutthe induction of ventricular tachycardia or ventricular fibrillation andthe ventricular refractory period was reached, the strength of the S2was increased by 10 mA and scanning was repeated. Once ventriculartachycardia or fibrillation was initiated and halted by cardioversion ordefibrillation, the procedure was repeated using a new S1 site with theinitial S2 strength set equal to that which induced the arrhythmia atthe previous S1 site. This protocol was repeated at all four S1 sites.After ventricular dysrhythmias were initiated from all four S1 sites,the strength of the S2 was increased in 10 mA steps to a maximum of 100mA for one of the S1 pacing sites.

Histological Examination

At the end of each experiment, the heart was excised, weighed and fixedin formalin. A histological section was taken perpendicular to theepicardium through the center of the infarct zone beneath the recordingplaque to determine the thickness of the infarcted and of thesubepicardially spared myocardium. On either side of this perpendicularsection, serial sections were taken every 0.5 mm parallel to theepicardium in the infarct zone to determine fiber orientating of thespared epicardial tissue. All sections were stained with hematoxylin andeosin.

Data Analysis

The recordings from each channel were displayed on a Sun 3/60 computerwork station. In all dogs the last two activations of the S1 train andall activations after the S2 stimulus until the ventricular tachycardiasettled into uniform repeatable complexes on the surface ECG wereanalyzed. If ventricular fibrillation instead of ventricular tachycardiawas induced, the initial six activation complexes after the S2 stimuluswere chosen for analysis. The time selected for each activation was thefastest slope for hiphasic complexes and the absolute peak value formonophasic and multiphasic complexes. T. Funada et al., Med. Biol. Eng.Comput. 21, 418 (1983). Electrodes with saturated signals or withsignals too noisy to identify activations reliably were not analyzed.Isochronal maps were drawn for all complexes analyzed. A heavy black barwas used to indicate block between neighboring electrodes if 1)activation times differed by more than 40 ms (conduction velocity <0.1m/sec), (15-17) and 2) double activations were seen in the electrodesbordering the line of block, in which one complex corresponded in timeto the activation front on one side of the block and the other complexcorresponded to the activation front on the other side of the line ofblock. Hatched bars were used to represent the "frame lines" betweensequential isochronal maps. The term "frame line" is used to indicatethat the activation front does not stop at the line but rather the framelines represent the break points between maps that are necessary torepresent the dynamic continuous activation sequence of reentry by aseries of static discrete isochronal maps.

With voltage dividers (see P. Wolf et al., supra), potentials weremeasured at the 121 recording electrodes for 10 ms monophasic shocksequal in strength to the lowest current inducing the tachyarrhythmia atall four S1 sites. Potentials were also recorded for stronger shocks inincrements of 20 mA to a maximum of 100 mA. unipolar potentials weremeasured at each recording site, relative to the preceding baseline, ata consistent point 3-4 ms into the shock. A 10 ms stimulus was used tomeasure the S2 potentials instead of the 5 ms stimulus used for S2induction of the arrhythmia because a short spike, lasting 1-2 ms, waspresent in the recordings at the onset and the offset of the S2stimulus. The potential gradient was calculated from the potentials andthe inter-electrode distances using a finite element method. D. Frazieret al., Circ. Res. 63, 147 (1988).

Statistical Procedures

Student's t test was used to analyze differences in means. Chi-squarewas used to analyze differences in populations. Data are presented asmean ±SD. Significance was defined as p≦0.05.

Results

Twelve mongrel dogs weighing 23.5±1.6 kg were the subjects of thisstudy. One of the twelve died in the first twelve hours post LADocclusion. A second dog died four days postinfarction during anesthesiainduction for the placement of electrodes. Therefore, arrhythmiainduction was attempted in ten animals. In two of the ten dogs, the S2threshold for ventricular arrhythmia (sustained ventricular tachycardiaor ventricular fibrillation) induction had only been determined for oneof the S1 pacing sites before the animals died. In the remaining eightanimals, the S2 arrhythmia threshold stimulus was determined for allfour S1 pacing sites. Thus, the S2 arrhythmia threshold stimulus wasdetermined for a total of 34 sites in the ten animals (Table 1).Sustained monomorphic ventricular tachycardia was induced from 24 ofthese sites, ventricular fibrillation from nine sites and sustainedpolymorphic ventricular tachycardia was induced from one S1 site. Theepisode of polymorphic ventricular tachycardia was eliminated from allstatistical analysis. By chi-square analysis the incidence ofmonomorphic ventricular tachycardia was significantly different fromventricular fibrillation (p=0.03).

                  TABLE 1                                                         ______________________________________                                        Number of S1 Sites Inducing                                                   Ventricular Tachyarrhythmias                                                                                  Transmural                                    Dog           Number of Sites   Extent of                                     Number   with SMVT     with VF  Infarct                                       ______________________________________                                        1        4             0        70%                                           2        4             0        70%                                           3        4             0        80%                                           4        4             0        80%                                            5*      1             0        90%                                           6        3             1        80%                                           7        .sup. 2.sup.+ 1        80%                                           8        2             2        30%                                           9        0             4        20%                                           10*      0             1        10%                                           ______________________________________                                         *Died after first arrhythmic event                                            .sup.+ Polymorphic VT from an additional S1 site                              SMVT = Sustained Monomorphic Ventricular Tachycardia                          VF = Ventricular Fibrillation                                            

FIG. 7 shows an example of monomorphic ventricular tachycardia inducedin a dog with an 80% transmural infarct. The S1 pacing site was theright ventricular free wall and the S2 stimulus was 20 mA, which is thelowest strength S2 stimulus that induced tachycardia in this animal. Theactivation front initiated by S1 stimulation enters from the upper leftcorner which is the area closest to the S1 pacing site (FIG. 7A). Thefront then conducts diagonally across the tissue under the plaque,following the long axis of the myocardial fibers. The earliestactivations after S2 stimulation are recorded on the left side of theplaque toward the S1 site (FIG. 7B), which is more recovered than theright and bottom sides at the time of S2 stimulation. The activationfronts then conduct to the right around both sides of a line of block(represented by the heavy black bar). There is a 71 ms time differencebetween the latest activation time recorded in the initial ventriculartachycardia beat (FIG. 7B) and the earliest activation time recorded inthe next beat (FIG. 7C) and double complexes are recorded at thesesites. Therefore, block is assumed present between the late site in FIG.7B and the adjacent early sites in FIG. 7C, so that it is not clear howor if the first beat conducted to the second. The fact that earliestactivation sites for the second ventricular tachycardia beat are not atthe edge of the plaque as for the first beat, but are next to the lineof assumed block, raises the possibility that reentry did occur,although it was undetected in the recordings. Activation then sweepsaround the upper line of block and possibly sweeps also around the lowerline of block although this is not definite because the lower line ofblock extends to the edge of the plaque (FIG. 7C). The latest activationtine in this beat is 31 ms before the earliest activation time recordedin the third tachycardia beat (FIG. 7D) and double complexes are nolonger observed in this region. Thus reentry is assumed to occur betweenthese two beats. The central line in FIG. 7C is shown solid to the leftand hatched to the right to represent block between beats 1 (FIG. 7B)and 2 (FIG. 7C) and reentry between beats 2 (FIG. 7C) and 3 (FIG. 7D).The hatched line is a frame line between successive panels that isnecessary to represent reentry by a series of isochronal maps. A similaractivation pattern is seen for the next three beats (FIG. 7D-F) withslight changes in the lines of block from beat to beat. By the fifthbeat, the lower line of block has shortened, so that a clear figure of 8reentry pattern is present (FIG. 7F). The tachycardia was stable afterthe fifth beat with only minimal changes in the frame and block lines insubsequent activation sequences. Conduction through the isthmusstabilized after the seventh beat.

In 19 of the 33 episodes of ventricular tachyarrhythmias induced bystimulation from the various S1 pacing sites, it was possible toidentify the initial activation sites of the first beat of thearrhythmia. Earliest post S2 activation was never recorded from theregion immediately adjacent to the S2 electrode. In 14 of these 19episodes initial activation occurred somewhere between the S1 and the S2stimulation site and generally conducted in the direction away from theS2 electrode and towards the S1 electrode, in the opposite direction tothe S1 activation sequence (FIG. 8, 9). In the other 5 episodes theinitial post S2 activation of the arrhythmia seemed to conduct into therecording area from outside the plaque (FIG. 7B). In the remainingarrhythmia episodes, the initial activation sites of the firstarrhythmia beat could not be identified because of post S2 stimulationsaturation of a large percentage of the recording electrodes. However,by the second beat it could be identified that the activation front wasin the opposite direction of the S1 activation sequence in 25 of the 33arrhythmia episodes.

Comparison of Ventricular Tachycardia and Fibrillation Induction

Sustained monomorphic ventricular tachycardia was the only arrhythmiainduced in five dogs. In these animals, the mean transmural infarctextent was 80% (Table 1). Ventricular fibrillation was the onlyarrhythmia induced in two dogs. In these animals, the mean transmuralextent of the infarct was 15%. Both ventricular tachycardia andfibrillation were induced in three dogs where the transmural extent ofthe infarct was 63%.

Conclusions

These data show that the more transmural the infarct and the thinner thelayer of spared epicardial tissue, the more likely the figure of 8reentry pattern will have a longer cycle length and result inventricular tachycardia rather than ventricular fibrillation.

The foregoing examples are illustrative of the present invention, andare not to be construed as limiting thereof. The invention is defined bythe following claims, with equivalents of the claims to be includedtherein.

That which is claimed is:
 1. A closed-heart method for treatingventricular tachycardia in a myocardial infarct patient afflicted withventricular tachycardia, said method comprising:(a) defining a thinlayer of spared myocardial tissue positioned between the myocardialinfarct scar tissue and the inner surface of the myocardium (theendocardium) of said patient wherein said defining step comprises thestep of defining a thin layer having an endocardial surface area of atleast 15 square centimeters; and then (b) ablating said thin layer ofspared myocardial tissue by a closed-heart procedure with an ablationcatheter so that said thin layer has an endocardial surface area of lessthan 15 square centimeters.
 2. A method according to claim 1, whereinsaid defining step comprises the step of defining a thin layer having athickness of up to about 5 millimeters.
 3. A method according to claim1, wherein said defining step comprises the step of defining a thinlayer having a thickness of from about 0.25 to 2 millimeters.
 4. Amethod according to claim 1, wherein said defining step comprises thestep of defining a thin layer having an endocardial surface area of fromabout 20 to 40 square centimeters.
 5. A method according to claim 1,wherein said defining step is carried out in the absence of ventriculartachycardia.
 6. A method according to claim 1, wherein said definingstep is carried out by detecting said thin layer of spared myocardialtissue by echocardiography.
 7. A method according to claim 1, whereinsaid defining step is carried out by detecting said infarct overlyingsaid thin layer of spared myocardial tissue by echocardiography.
 8. Amethod according to claim 1, wherein said defining step is carried outby visualization of endocardial fibrosis beneath said thin layer ofspared myocardial tissue.
 9. A method according to claim 1, wherein saiddefining step is carried out by electrically stimulating the endocardiumto detect an increased pacing threshold.
 10. A method according to claim1, wherein said defining step is carried out with a catheter mountedechocardiographic ultrasound crystal sensor inserted into the interiorof the heart of said patient.
 11. A method according to claim 1, whereinsaid defining step is carried out with an echocardiographic ultrasoundcrystal sensor positioned in the esophagus of said patient.
 12. A methodaccording to claim 1, wherein said ablating step comprises destroyingall of said thin layer of spared myocardial tissue.
 13. A methodaccording to claim 1, wherein said ablating step comprises the step ofelectrically separating a portion of said thin layer sufficient in sizeto combat ventricular tachycardia from the remainder of the endocardium.14. A method according to claim 13, wherein said electrically separatingstep comprises the step of creating a continuous lesion extending fromthe endocardium to said myocardial infarct scar tissue around said thinlayer of spared myocardial tissue, said continuous lesion encirclingsaid thin layer to electrically separate said thin layer from adjacentmyocardial tissue.
 15. A method according to claim 1, wherein saidablating step comprises the step of creating at least one elongatelesion in said thin layer extending from the endocardium to saidmyocardial infarct scar tissue, wherein said at least one elongatelesion divides said thin layer into a plurality of electricallyseparated portions, and wherein each of said portions is incapable oforiginating ventricular tachycardia.
 16. A method according to claim 15,wherein said at least one elongate lesion comprises a plurality ofelongate lesions.
 17. A method according to claim 1, wherein saidablating step is followed by the step of verifying that said thin layerof spared myocardial tissue is no longer capable of originating aventricular tachycardia.
 18. A method according to claim 17, whereinsaid verifying step comprises a programmed pacing technique to induceventricular tachycardia.
 19. A closed-heart method for treatingventricular tachycardia in a myocardial infarct patient afflicted withventricular tachycardia, said method comprising:(a) defining a thinlayer of spared myocardial tissue positioned between the myocardialinfarct scar tissue and the inner surface of the myocardium (theendocardium) of said patient, said thin layer having a thickness up toabout five millimeters and an endocardial surface area of at least 15square centimeters; and then (b) ablating said thin layer of sparedmyocardial tissue by creating at least one elongate lesion in said thinlayer extending from the endocardium to said myocardial infarct scartissue in a closed-heart procedure with an ablation catheter, whereinsaid at least one elongate lesion is configured to reduce any portion ofsaid thin layer in electrical contact with the remainder of theendocardium to a size, in endocardial surface area, sufficient to combatventricular tachycardia in said patient and less than 15 squarecentimeters.
 20. A method according to claim 19, wherein said ablatingstep comprises the step of electrically separating from the remainder ofthe endocardium a portion of said thin layer sufficient in size, insurface area to combat ventricular tachycardia.
 21. A method accordingto claim 19, wherein said electrically separating step comprises thestep of creating a continuous lesion extending from the endocardium tosaid myocardial infarct scar tissue around said thin layer of sparedmyocardial tissue, said continuous lesion encircling said thin layer toelectrically separate said thin layer from adjacent myocardial tissue.22. A method according to claim 19, wherein said ablating step comprisesthe step of creating at least one elongate lesion in said thin layerextending from the endocardium to said myocardial infarct scar tissue,wherein said at least one elongate lesion divides said thin layer into aplurality of electrically separated portions, and wherein each of saidportions is reduced to a size, in surface area, sufficient to combatventricular tachycardia.
 23. A method according to claim 19, whereinsaid at least one elongate lesion comprises a plurality of elongatelesions.
 24. A method for prognosing the likelihood of ventriculartachycardia occurring in a myocardial infarct patient not previouslydiagnosed as afflicted with ventricular tachycardia, said methodcomprising detecting a thin layer of spared myocardial tissue positionedbetween the myocardial infarct scar tissue and the inner surface of themyocardium (the endocardium) in said patient, and;determining that saidthin layer has an endocardial surface area of at least 15 squarecentimeters.
 25. A method according to claim 24, wherein said method isa closed-heart method.
 26. A method according to claim 24, wherein saiddetecting step is carried out by:(a) determining if a thin layer ofspared tissue exists between the infarct and the endocardium, and then(b) creating a map of the locations of the thin layer identified in saiddetermining step to define the thin layer areas, and (c) evaluating thedimensions of said thin layer areas to determine if the contiguousportions of said thin layer areas are of sufficient size to supportreentrant pathways.
 27. A method according to claim 24, wherein saiddetecting step comprises the step of detecting a thin layer having athickness of up to about 5 millimeters.
 28. A method according to claim24, wherein said detecting step comprises the step of detecting a thinlayer having a thickness of from about 0.25 to 2 millimeters.
 29. Amethod according to claim 24, wherein said detecting step comprises thestep of detecting a thin layer having an endocardial surface area offrom about 20 to 40 square centimeters.
 30. An apparatus for theablation treatment of ventricular tachycardia, comprising:anintraventricular catheter; detecting means for detecting a thin layer ofspared endocardial tissue connected to said intraventricular catheter;determining means for determining that said thin layer has anendocardial surface area of at least 15 square centimeters; ablationmeans for ablating said thin layer of spared endocardial tissueconnected to said intraventricular catheter; and analyzing meansoperatively associated with said detecting means for prognosing thelikelihood of ventricular tachycardia arising from said thin layer.